The effect of dipeptidyl peptidase-4 inhibitor on incidence and clinical course in bullous pemphigoid patients in a tertiary medical center.

Several studies have reported an association between dipeptidyl peptidase 4 inhibitor (DPP4i), a commonly prescribed second-line oral antihyperglycemic drug, and bullous pemphigoid (BP). However, the benefits of DPP4i withdrawal in patients with BP remain controversial. This study primarily aimed to evaluate the clinical severity of DPP4i-associated BP by comparing it to those without Type 2 diabetes mellitus (DM). The secondary objective was to determine whether cessation of DPP4i is necessary for all patients with BP. This retrospective case-control study included 83 patients. The participants were divided into three groups according to their diabetic status and the status of discontinuance or continuance of DPP4i. The 12-month follow-up of the monthly dosage of systemic steroids per body weight (kg) and the percentage of systemic steroid off-therapy in these participants were recorded since the diagnosis of BP. Compared to patients with BP without DM, the 1st, 3rd, and 12th systemic prednisolone doses were significantly lower in the DPP4i group (p = 0.01684, 0.02559, and 0.009336, respectively). The 12th systemic prednisolone dose was significantly lower in patients who discontinued DPP4i (p = 0.0338). Nevertheless, several spontaneous remissions with systemic steroid off-therapy were also noted in the DPP4i-continuance group within 12 months of follow-up. This article supports the favorable impact of DPP4i withdrawal in patients with BP and shows that DPP4i may incite or aggravate BP, resulting in a milder disease course.

Learning strategy differentially impacts memory connections in children and adults.

Even once children can accurately remember their experiences, they nevertheless struggle to use those memories in flexible new ways-as in when drawing inferences. However, it remains an open question as to whether the developmental differences observed during both memory formation and inference itself represent a fundamental limitation on children's learning mechanisms, or rather their deployment of suboptimal strategy. Here, 7-9-year-old children (N = 154) and young adults (N = 130) first formed strong memories for initial (AB) associations and then engaged in one of three learning strategies as they viewed overlapping (BC) pairs. We found that being told to integrate-combine ABC during learning-both significantly improved children's ability to explicitly relate the indirectly associated A and C items during inference and protected the underlying pair memories from forgetting. However, this finding contrasted with implicit evidence for memory-to-memory connections: Adults and children both formed A-C links prior to any knowledge of an inference test-yet for children, such links were most apparent when they were told to simply encode BC, not integrate. Moreover, the accessibility of such implicit links differed between children and adults, with adults using them to make explicit inferences but children only doing so for well-established direct AB pairs. These results suggest that while a lack of integration strategy may explain a large share of the developmental differences in explicit inference, children and adults nevertheless differ in both the circumstances under which they connect interrelated memories and their ability to later leverage those links to inform flexible behaviours. RESEARCH HIGHLIGHTS: Children and adults view AB and BC pairs related through a shared item, B. This provides an opportunity for learners to connect A-C in memory. Being encouraged to integrate ABC during learning boosted performance on an explicit test of A-C connections (children and adults) and protected from forgetting (children). Children and adults differed in when implicit A-C connections were formed-occurring primarily when told to separately encode BC (children) versus integrate (adults), respectively. Adults used implicit A-C connections to facilitate explicit judgments, while children did not. Our results suggest developmental differences in the learning conditions promoting memory-to-memory connections.

Favorable effect after single treatment session of 755-nm-picosecond laser with a diffractive optic lens on facial wrinkles and pore size in Asians.

OBJECTIVES: Laser therapy has become one of the mainstay treatments for improving signs of aging including wrinkles, large pores, and skin pigmentation. However, in patients with pigmented skin, an increase in complications including post-inflammatory hyperpigmentation (PIH) has been noted. The purpose of this study is to investigate not only the safety profile of 755-nm picosecond laser with diffractive lens array (DLA) at approximately 2250 pulses on the face in people with darker skin, but also to evaluate its efficacy in treating wrinkles and pore sizes after one treatment session among different age groups. METHODS: This single-center, retrospective study enrolled patients between age 22 and 65 with both facial wrinkles and enlarged pore sizes. A total of 46 patients (7 male, 39 female, mean age 43) with Fitzpatrick skin types III and IV were enrolled. Two independent data-blinded dermatologists assessed and scored the improvements of patients' wrinkles and pore sizes using photographs. RESULTS: After one treatment session, statistically significant improvements were observed in lateral canthal wrinkles (p < 0.001) and facial wrinkles (p = 0.014). In addition, greater percentage of the patients from the aged group (50-65 years) showed clinically significant improvement as compared with the younger group. CONCLUSIONS: For patients with type III and IV skin, one session of DLA picosecond laser treatment at around 2250 pulses to the face is safe and effective for clinically meaningful improvement of the wrinkles and pore sizes, especially for the patients from 50- to 65-years of age.

Mathematical modeling of the influence of cultural practices on cholera infections in Cameroon.

The Far North Region of Cameroon, a high risk cholera endemic region, has been experiencing serious and recurrent cholera outbreaks in recent years. Cholera outbreaks in this region are associated with cultural practices (traditional and religious beliefs). In this paper, we introduce a mathematical model of the influence of cultural practices on the dynamics of cholera in the Far North Region. Our model is an SEIR type model with a pathogen class and multiple susceptible classes based on traditional and religious beliefs. Using daily reported cholera cases from three health districts (Kaélé, Kar Hay and Moutourwa) in the Far North Region from June 25, 2019 to August 16, 2019, we estimate parameter values of our model and use Akaike information criterion (AIC) to demonstrate that our model gives a good fit for our data on cholera cases. We use sensitivity analysis to study the impact of each model parameter on the threshold parameter (control reproduction number), Rc, and the number of model predicted cholera cases. Finally, we investigate the effect of cultural practices on the number of cholera cases in the region.

A discrete-time risk-structured model of cholera infections in Cameroon.

In a recent paper, Che et al. [5] used a continuous-time Ordinary Differential Equation (ODE) model with risk structure to study cholera infections in Cameroon. However, the population and the reported cholera cases in Cameroon are censored at discrete-time annual intervals. In this paper, unlike in [5], we introduce a discrete-time risk-structured cholera model with no spatial structure. We use our discrete-time demographic equation to 'fit' the annual population of Cameroon. Furthermore, we use our fitted discrete-time model to capture the annually reported cholera cases from 1987 to 2004 and to study the impact of vaccination, treatment and improved sanitation on the number of cholera infections from 2004 to 2019. Our discrete-time cholera model confirms the results of the ODE model in [5]. However, our discrete-time model predicts a decrease in the number of cholera cases in a shorter period of cholera intervention (2004-2019) as compared to the ODE model's period of intervention (2004-2022).

Effects of Solanum undatum extract (SR-T100) on photocarcinogenesis and photoaging of actinic keratosis.

SR-T100 gel, containing solamargine extracted from Solanum undatum (synonym: Solanum incanum), had good therapeutic effects on actinic keratosis (AK) in human and ultraviolet B-induced papilloma in mice. This study aimed to investigate the immunohistochemical changes in the human skin after SR-T100 treatment. An immunohistochemical study was performed and the changes in photocarcinogenesis and photoaging markers after 16-week SR-T100 gel treatment were documented. SR-T100 gel treatment for 16 weeks resulted in complete remission in nine AK lesions and partial remission in four AK lesions. SR-T100 gel abolished the expression of mutant p53 and SOX2 and restored the expression of NOTCH1. Additionally, SR-T100 gel improved wrinkling in human skin, while restoring the expression of lamin B1 and increasing synthesis of new elastic fibers. SR-T100 gel had therapeutic effects on photocarcinogenesis and photoaging of photodamaged skin with AK.

Risk structured model of cholera infections in Cameroon.

Since 1991, Cameroon, a cholera endemic African country, has been experiencing large cholera outbreaks and cholera related deaths. In this paper, we use a "fitted" demographic equation (disease-free equation) to capture the total population of Cameroon, and then use a fitted low-high risk structured cholera differential equation model to study reported cholera cases in Cameroon from 1987 to 2004. For simplicity, our model has no spatial structure. The basic reproduction number of our fitted cholera model, R0, is bigger than 1 and our model predicted cholera endemicity in Cameroon. In addition, the fitted risk structured model predicted a decreasing trend from 1987 to 1994 and an increasing trend from 1995 to 2004 in the pre-intervention reported number of cholera cases in Cameroon from 1987 to 2004. Using the fitted risk structured cholera model, we study the impact of vaccination, treatment and improved sanitation on the number of cholera infections in Cameroon from 2004 to 2022. The dual strategies of either vaccination and treatment or vaccination and improved sanitation or the combined strategy of vaccination, treatment and improved sanitation reduce the basic reproduction number of Cameroon from 1.1803 to 0.9982, 1.1803 to 0.9987 and 1.1803 to 0.9952, respectively, and the number of cholera cases by 99.6735%, 98.7498% and 99.7280%, respectively. Thus, each of these three strategies is capable of eliminating cholera in Cameroon with the combined strategy having the lowest value for the effective reproduction number, RE, and the highest percentage decrease in the number of cholera cases. Finally, using sensitivity analysis, we study the impact of our model parameters on the demographic threshold, basic reproduction number, effective reproduction number and on the total number of our model's predicted cholera cases.

Concentration-dependent cellular responses of arsenic in keratinocytes.

Arsenic (As) is considered as a human carcinogen or tumor-promoting agent. Epidemiological evidences indicated that cancer incidences of residents in arseniasis areas were significantly higher in multiple organs, including urinary bladder, lungs, and especially the skin, than those living in non-arseniasis areas. In the context of skin cancers, keratinocytes are believed to be the main target cells in As carcinogenesis. Therefore, we discuss the significance of keratinocyte-specific effects of As on skin carcinogenesis. As is known to be cytotoxic because of its chemical reactions with the thiol group of proteins and its ability to generate free radicals during cellular metabolism. However, at relatively low concentrations, As shows stimulatory effects, such as cell activation and proliferation. Because long-term As exposure is associated with skin carcinogenesis, we reviewed the mechanisms of As-induced keratinocyte dysfunctions by means of time- and concentration-dependent cellular responses. The mechanisms and interactions underlying As-induced keratinocyte dysfunctions not only provide a model of As in skin carcinogenesis process but also help in understanding the regulation of As carcinogenesis in other internal organs.

Solanum incanum extract (SR-T100) induces human cutaneous squamous cell carcinoma apoptosis through modulating tumor necrosis factor receptor signaling pathway.

BACKGROUND: The Solanum species herbs have been used to treat cancer for centuries; however, the underlying mechanisms and effectiveness in vivo remain unclear. OBJECTIVES: SR-T100, extracted from the Solanum incanum, contains solamargine alkaloid as the main active ingredient. Here, we investigated the apoptosis-inducing effects of SR-T100 for targeting squamous cell carcinoma (SCC) in vitro and in vivo. METHODS: We elucidated the mechanism by which SR-T100 induces apoptosis of human SCCs (A431, SCC4, SCC9, and SCC25) cells. The efficacy and safety issues were addressed regarding topical treatment of SR-T100 on UVB-induced cutaneous SCC of hairless mice and actinic keratoses (AKs) of human. RESULTS: SR-T100 induces apoptosis in human SCCs cell lines by up-regulating the expressions of tumor necrosis factor receptors (TNFRs) and Fas, and downstream adaptors FADD/TRADD of the TNF-α and Fas ligand signaling cascades. SR-T100 also triggered the mitochondrial apoptotic pathway, as up-regulated cytochrome c and Bax, down-regulated Bcl-X(L). Animal experiments showed that all papillomas (35/35) and 27 of 30 UVB-induced microinvasive SCCs in hairless mice disappeared within 10 weeks after once-daily application of topical SR-T100. Furthermore, 13 patients, who suffered with 14 AKs, were treated with once-daily topical SR-T100 gel and 10 AKs cured after 16 weeks, showing negligible discomforts. CONCLUSION: Our studies indicate that SR-T100 induces apoptosis of SCC cells via death receptors and the mitochondrial death pathway. The high efficacy of SR-T100 in our preclinical trial suggests that SR-T100 is a highly promising herb for AKs and related disorders.

Narrow-band UVB treatment of vitiligo in Chinese.

Narrow-band ultraviolet B (NBUVB) phototherapy has recently been reported to be an effective and safe treatment modality for vitiligo. In the present report, we evaluated the efficacy and safety of NBUVB therapy for vitiligo in Chinese patients. Seventy-two vitiligo patients treated from 2000 to 2003, were included retrospectively (male: female=33:39, mean age: 38.5). Among them, 61 were non-segmental type and 11 the segmental type. Treatments were given two to three times a week for a maximum period of one year with an initial dose of 0.2 J/cm2 and a 0-20% increment each session (mean accumulation dose: 155.3 J/cm2). Computer image analysis by Supervise classification was used to estimate the area of vitiligo involvement before and after treatment. An excellent response (75-100% area of repigmentation) was obtained in 9 patients (12.5%) and a good response (50-75%) in 24 (33.3%), a moderate response (25-50%) in 20 (27.8%), and a poor response (0-25%) in 19 (26.4%). In summary, 45.8% of our patients had more than 50% repigmentation. Burns were a side effect in 5 patients (7%) and transient erythema with itching or xerosis was noted in 5 patients (7%). These results indicate that NBUVB phototherapy is an effective and safe treatment choice for generalized vitiligo.